A study by Cincinnati Children’s Hospital Medical Center in Ohio reveals that a protein called Argonaute 2 (AGO2) controls how energy is made and used in the liver.
It does this by silencing RNA, a molecule that carries genetic instructions held in the DNA blueprints in the cell’s nucleus to the cell’s protein-making machinery.
The scientists revealed that, by silencing RNA, AGO2 slows metabolism in the liver and the organ’s “ability to process a high-fat diet.”
However, when they deleted AGO2 in the livers of mice on a high-fat diet, the mice did not become obese and did not develop type 2 diabetes and fatty liver disease.
Fatty liver disease — or, more accurately, nonalcoholic fatty liver disease — is a condition in which fat builds up in the liver. It can severely harm the organ, whose main job is to clean and detoxify blood.
Vicious cycle in disrupted energy metabolism
The findings suggest that RNA silencing by AGO2 links two important processes: control of energy supply, and the production of proteins inside cells.
“This mechanism,” note the investigators in a recently published Nature Communications paper on their work, “may be the core of a vicious cycle in disrupted energy metabolism in the obese liver.”
The team identified AGO2 after screening and analyzing the behavior of genes and the associated proteins that they target in the liver.
They examined the effect of deleting proteins that play a key role in liver metabolism in normal and genetically engineered mice that were fed on high-fat diets.
Senior study author Takahisa Nakamura, an assistant professor in the Department of Pediatrics at Cincinnati Children’s Hospital, warns that the science is “still basic,” and that it is too early to say how it might translate into new treatments.
There might be important implications, however, for the treatment of “chronic metabolic disorders like diabetes, fatty liver diseases, and other obesity-associated illnesses,” he notes.
What they have achieved so far, Nakamura suggests, should help them search for potential new treatments that target obesity and associated diseases by altering energy balance in the liver.
Further work will involve the confirmation of these findings in “laboratory models” and the development of an experimental AGO2 blocker for clinical testing in humans.
The obesity epidemic and calorie imbalance
Obesity is a global public health problem that has reached epidemic proportions. Most people in the world now live in countries where carrying too much weight is more fatal than being underweight.
The issue has arisen due to a calorie imbalance; we are consuming more — but burning fewer — calories now than we did a few decades ago.
The main reason that we are taking in more calories is because there has been a worldwide increase in consumption of energy-dense foods — particularly those that are high in fat.
Also, we are burning fewer calories because we move and exert ourselves much less than our forefathers did; we increasingly use motorized transport and have more sedentary jobs and lifestyles.
The results of the new study suggest that one way to tackle this could be to alter metabolism in people’s livers, as the liver is a “major organ for energy consumption.”
The study focuses on protein production in cells, which is one of the processes in the liver that needs a lot of energy. This accounts for up to 30 percent of energy used in the liver.